This study is designed to continue our investigation of the mechanism of fluoride incorporation into developing enamel, especially as it si related to fluoride binding by the enamel matrix proteins, and to further define the physiologic and potentially pathologic influence of fluoride in matrix loss and mineralization during enamel formation. The project is a logical extension of our work being conducted with the support of our currently funded grant DE05289. The results of those studies to this point have allowed us to establish several important parameters of the F- binding system demonstratee Ca2+ binding by the matrix, show effects of F- on 45Ca transport through the enamel organ and on the rate of enamel mineralization, and to propose a physiologic function for the F- binding system. We propose to continue the work according to four specific aims: (1) to determine, using autoradiographic methods, the comparative uptake of 45Ca and 18F in developing rat molar enamel when mineralization of the newly deposited matrix has been inhibited by cobalt; (2) to determine by proton activation analysis at which stage in enamel development the enamel surface-inward fluorine concentration gradient is established; (3) to determine if the fluoride effect of retarding the breakdown of high molecular weight matrix proteins is related to possible action as a protease inhibitor or by physical-chemical stabilization of the protein; and (4) to determine if fluoride is released when the high molecular weight matrix proteins are hydrolyzed by a protese in vitro. The results of the work will allow us to explore the validity of four hypotheses that describe a new concept for the means by which fluoride is incorporated into developing enamel and the mechanism by which it acts on enamel to impart caries resistance and fluorosis.